Melatonin counteracts oxidative damage in lens by regulation of Nrf2 and NLRP3 inflammasome activity

2021 ◽  
pp. 108912
Author(s):  
Victoria Eugenia Lledó ◽  
Hanan Award Alkozi ◽  
Juan Sánchez-Naves ◽  
Miguel Angel Fernandez-Torres ◽  
Ana Guzman-Aranguez
Keyword(s):  
Oxidative Damage ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activity

scholarly journals Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Faith L. Anderson ◽  
Katharine M. von Herrmann ◽  
Angeline S. Andrew ◽  
Yuliya I. Kuras ◽  
Alison L. Young ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Inflammasome Activation ◽  
Membrane Pore ◽  
Related Proteins ◽  
Inflammasome Activity

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD.

Snail-Regulated Exosomal MicroRNA-21 Suppresses NLRP3 Inflammasome Activity to Enhance Chemoresistance

2021 ◽  
Author(s):  
Han-Ying Cheng ◽  
Chia-Hsin Hsieh ◽  
Shyh-Kuan Tai ◽  
Pen-Yuan Chu ◽  
Po-Han Lin ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Nlrp3 Inflammasome ◽  
Epithelial Mesenchymal Transition ◽  
Resistant Mutant ◽  
Mesenchymal Transition ◽  
Response To Chemotherapy ◽  
Drug Resistant Mutant ◽  
Pros And Cons ◽  
Exosomal Microrna ◽  
Inflammasome Activity

Abstract Compared to the precise targeting of drug-resistant mutant cancer cells, strategies for eliminating non-genetic adaptation-mediated resistance are limited. The pros and cons of the existence of inflammasomes in cancer have been reported. Nevertheless, the dynamic response of inflammasomes to therapies should be addressed. Here, we have demonstrated that in cancer cells undergoing Snail-induced epithelial-mesenchymal transition (EMT), tumor cells suppress NLRP3 inflammasome activities of tumor-associated macrophages (TAMs) in response to chemotherapy through the delivery of exosomal microRNA (miR)-21. Mechanistically, miR-21 represses PTEN and BRCC3 to facilitate NLRP3 phosphorylation and lysine-63 ubiquitination, inhibiting NLRP3 inflammasome assembly. Furthermore, the Snail-miR-21 axis shapes the post-chemotherapy tumor microenvironment (TME) by repopulating TAMs and by activating CD8+ T cells. In head and neck cancer patients, the Snail-high cases lacked post-chemotherapy IL-1β surge and were correlated with a worse response. This finding reveals the mechanism of EMT-mediated resistance beyond cancer stemness through modulation of post-treatment inflammasome activity. It also highlights the dynamic remodeling of the TME throughout metastatic evolution.

scholarly journals ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells

2021 ◽  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Hypoxia Inducible Factor ◽  
Bronchial Epithelial Cells ◽  
Inflammasome Activation ◽  
Bronchial Epithelial ◽  
Asthmatic Patients ◽  
Pediatric Diseases ◽  
Inflammasome Activity

Introduction: Childhood asthma is one of the most common pediatric diseases, and its incidence is increasing. Annexin A3 (ANXA3) is a member of the Annexin family, a well-known polygenic family of membrane binding proteins. Bioinformation analysis showed that ANXA3 was highly expressed in asthmatic patients, suggesting the effects of ANXA3 on asthma, whereas the mechanism is still unclear. Methods: A inflammatory response model of bronchial epithelial BEAS-2B cells induced by LPS was constructed. Immunoblot and quantitative PCR assays were performed to detect the expression levels of ANXA3 in control or LPS-induced BEAS-2B cells. MTT, flow cytometry (FCM), and Immunoblot assays were respectively conducted to detect the effects of ANXA3 on survival and apoptosis of LPS-induced BEAS-2B cells. qPCR and ELISA assays were performed to detect the expression of TNF-α, IL-6, and IL-8. Additionally, Immunoblot assays were performed to detect the effects of ANXA3 on HIF1α and NLRP3 inflammasome in BEAS-2B cells. Results: We found ANXA3 was overexpressed in LPS-induced BEAS-2B cells. ANXA3 ablation promoted the survival of LPS-induced BEAS-2B cells and suppressed the inflammatory response of LPS-induced BEAS-2B cells. Importantly, we noticed ANXA3 inhibited HIF1α-induced NLRP3 inflammasome activity, and increasing the expression of HIF-α rescued the effects of ANXA3 depletion on asthma. Conclusion: ANXA3 enhanced LPS-triggered inflammation of human bronchial epithelial cells by regulating hypoxia-inducible factor-1α (HIF1α)-mediated NLRP3 inflammasome activation, and thought ANXA3 as a promising molecular target for acute asthma treatment.

scholarly journals Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Bin Zheng ◽  
Shuncai Zhang ◽  
Yanlu Ying ◽  
Xinying Guo ◽  
Hengchang Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Nlrp3 Inflammasome ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Improvement Effect ◽  
Improved Performance ◽  
Inflammasome Activity ◽  
Adrenergic Receptor Agonist ◽  
Nlrp3 Activity

The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist that inhibits the activation of NLRP3. Thus, it was hypothesized that Dex could attenuate TBI by inhibiting NLRP3 inflammasome activity in hippocampus. Rats were subjected to controlled cortical impact method to induce TBI, and treated with Dex. The effect of Dex treatment on the cognitive function, NLRP3 activity, and microglial activation in rat brain tissues was assessed. The administration of Dex improved performance of TBI rats in Morris water maze (MWM) test, which was associated with the increased neurone viability and suppressed microglia activity. Moreover, the administration of Dex inhibited the neuroinflammation in brain tissue as well as the expressions of NLRP3 and caspase-1. Additionally, Dex and NLRP3 inhibitor, BAY-11-7082 had a synergistic effect in inhibiting NLRP3/caspase-1 axis activity and improving TBI. The findings outlined in the current study indicated that the improvement effect of Dex on TBI was related to its effect on NLRP3 activity.

scholarly journals P2845Colchicine reduces NLRP3 inflammasome activity in murine Coxsackievirus B3-induced myocarditis

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
S Van Linthout ◽  
K Pappritz ◽  
J Lin ◽  
M Sosnowski ◽  
M El-Shafeey ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Coxsackievirus B3 ◽  
Inflammasome Activity

Effects of antidiabetic drugs on NLRP3 inflammasome activity, with a focus on diabetic kidneys

2019 ◽  
Vol 24 (1) ◽  
pp. 256-262 ◽  
Author(s):  
Habib Yaribeygi ◽  
Niki Katsiki ◽  
Alexandra E. Butler ◽  
Amirhossein Sahebkar
Keyword(s):  
Nlrp3 Inflammasome ◽  
Antidiabetic Drugs ◽  
Inflammasome Activity

Targeting the Deubiquitinase STAMBP to Reduce NLRP3 Inflammasome Activity

2019 ◽  
Author(s):  
J.S. Bednash ◽  
T.R. Smail ◽  
J.D. Londino ◽  
B. Chen ◽  
R.K. Mallampalli
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activity

scholarly journals Intravenous Arginine Administration Downregulates NLRP3 Inflammasome Activity and Attenuates Acute Kidney Injury in Mice with Polymicrobial Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Sharon Angela Tanuseputero ◽  
Ming-Tsan Lin ◽  
Sung-Ling Yeh ◽  
Chiu-Li Yeh
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Kidney Function ◽  
Nlrp3 Inflammasome ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Major Complication ◽  
Receptor Protein ◽  
No Production ◽  
Inflammasome Activity

Acute kidney injury (AKI) is a major complication of sepsis. Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein complexes that mediate septic AKI. L-arginine (Arg) is a conditionally essential amino acid in catabolic conditions and a substrate for nitric oxide (NO) production; however, its use in sepsis is controversial. This study investigated the effect of intravenous Arg supplementation on modulating NLRP3 inflammasome activity in relation to septic AKI. Mice were divided into normal control (NC), sham, sepsis saline (SS), and sepsis Arg (SA) groups. In order to investigate the role of NO, L-N6-(1-iminoethyl)-lysine hydrochloride (L-NIL), an inducible NO synthase inhibitor, was administered to the sepsis groups. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg via tail vein 1 h after CLP. Mice were sacrificed at 6, 12, and 24 h after sepsis. The results showed that compared to the NC group, septic mice had higher plasma kidney function parameters and lower Arg levels. Also, renal NLRP3 inflammasome protein expression and tubular injury score increased. After Arg treatment, plasma Arg and NO levels increased, kidney function improved, and expressions of renal NLRP3 inflammasome-related proteins were downregulated. Changes in plasma NO and renal NLRP3 inflammasome-related protein expression were abrogated when L-NIL was given to the Arg sepsis groups. Arg plus L-NIL administration also attenuated kidney injury after CLP. The findings suggest that intravenous Arg supplementation immediately after sepsis restores plasma Arg levels and is beneficial for attenuating septic AKI, partly via NO-mediated NLRP3 inflammasome inhibition.

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